CN1414854B - 膦酸酯化合物 - Google Patents
膦酸酯化合物 Download PDFInfo
- Publication number
- CN1414854B CN1414854B CN00818111.XA CN00818111A CN1414854B CN 1414854 B CN1414854 B CN 1414854B CN 00818111 A CN00818111 A CN 00818111A CN 1414854 B CN1414854 B CN 1414854B
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- Prior art keywords
- virus
- phosphonate
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- ester
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- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/405—Esters of poly(thio)phosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
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- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
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- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US16881399P | 1999-12-03 | 1999-12-03 | |
US60/168,813 | 1999-12-03 | ||
US20571900P | 2000-05-19 | 2000-05-19 | |
US60/205,719 | 2000-05-19 | ||
PCT/US2000/033079 WO2001039724A2 (en) | 1999-12-03 | 2000-12-04 | Phosphonate compounds |
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CN1414854A CN1414854A (zh) | 2003-04-30 |
CN1414854B true CN1414854B (zh) | 2015-08-19 |
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CN00818111.XA Expired - Lifetime CN1414854B (zh) | 1999-12-03 | 2000-12-04 | 膦酸酯化合物 |
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US (14) | US6716825B2 (es) |
EP (1) | EP1233770B1 (es) |
JP (4) | JP4993649B2 (es) |
KR (1) | KR20020073342A (es) |
CN (1) | CN1414854B (es) |
AT (1) | ATE385797T1 (es) |
AU (3) | AU785355B2 (es) |
BR (1) | BR0016058A (es) |
CA (2) | CA2393410C (es) |
CY (1) | CY1107927T1 (es) |
DE (1) | DE60038038T2 (es) |
DK (2) | DK1914237T3 (es) |
ES (2) | ES2300281T3 (es) |
HK (1) | HK1050627B (es) |
MX (1) | MXPA02005490A (es) |
PT (2) | PT1233770E (es) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US12023348B2 (en) | 2016-04-26 | 2024-07-02 | The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center | EGR1 targeting molecules for the treatment of inflammatory and hyperproliferative conditions |
Families Citing this family (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7205404B1 (en) | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
ES2300281T3 (es) * | 1999-12-03 | 2008-06-16 | The Regents Of The University Of California At San Diego | Compuestos de fosfonato. |
US7163932B2 (en) * | 2001-06-20 | 2007-01-16 | Merck Frosst Canada & Co. | Aryldifluoromethylphosphonic acids for treatment of diabetes |
FR2837490B1 (fr) * | 2002-03-21 | 2009-04-17 | Univ Paris 13 | Nouveaux derives de bisphosphonates, leurs preparations et utilisations |
ATE455121T1 (de) * | 2001-07-16 | 2010-01-15 | Univ Paris 13 | Herstellungsverfahren von derivate von bisphosphonaten |
EP1490024B1 (en) * | 2002-03-06 | 2012-01-18 | EffRx Pharmaceuticals SA | Effervescent compositions comprising alendronate |
US7488496B2 (en) | 2002-03-06 | 2009-02-10 | Christer Rosen | Effervescent compositions comprising bisphosphonates and methods related thereto |
US7462608B2 (en) * | 2002-04-26 | 2008-12-09 | Gilead Sciences, Inc. | Non nucleoside reverse transcriptase inhibitors |
AU2003901813A0 (en) * | 2003-04-15 | 2003-05-01 | Vital Health Sciences Pty Ltd | Pharmaceutical derivatives |
US7407965B2 (en) | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
EP1620109A2 (en) | 2003-04-25 | 2006-02-01 | Gilead Sciences, Inc. | Kinase inhibitor phosphonate conjugates |
WO2005002626A2 (en) | 2003-04-25 | 2005-01-13 | Gilead Sciences, Inc. | Therapeutic phosphonate compounds |
US7432261B2 (en) | 2003-04-25 | 2008-10-07 | Gilead Sciences, Inc. | Anti-inflammatory phosphonate compounds |
US7452901B2 (en) | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
US7427636B2 (en) | 2003-04-25 | 2008-09-23 | Gilead Sciences, Inc. | Inosine monophosphate dehydrogenase inhibitory phosphonate compounds |
ATE490788T1 (de) | 2003-04-25 | 2010-12-15 | Gilead Sciences Inc | Antivirale phosphonate analoge |
WO2004096285A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-infective phosphonate conjugates |
US7470724B2 (en) | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
EP1678322A2 (en) | 2003-10-24 | 2006-07-12 | Gilead Sciences, Inc. | Methods and compositions for identifying therapeutic compounds |
WO2005044308A1 (en) | 2003-10-24 | 2005-05-19 | Gilead Sciences, Inc. | Phosphonate analogs of antimetabolites |
US7427624B2 (en) | 2003-10-24 | 2008-09-23 | Gilead Sciences, Inc. | Purine nucleoside phosphorylase inhibitory phosphonate compounds |
WO2005056019A1 (ja) * | 2003-12-12 | 2005-06-23 | Astellas Pharma Inc. | 悪性黒色腫治療剤 |
ATE424400T1 (de) | 2003-12-22 | 2009-03-15 | Gilead Sciences Inc | 4'-substituierte carbovir- und abacavir-derivate sowie verwandte verbindungen mit hiv- und hcv- antiviraler wirkung |
WO2005090370A1 (en) * | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Pharmacologically active agents containing esterified phosphonates and methods for use thereof |
WO2006076015A2 (en) * | 2004-04-30 | 2006-07-20 | The Regents Of The University Of California | 1-[2-(phosphonomethoxy)ethyl]-cytosine and analogs thereof |
DE602005027466D1 (de) | 2004-07-27 | 2011-05-26 | Gilead Sciences Inc | Nukleosid phosphonat konjugate als anti hiv mittel |
AU2005306612B2 (en) * | 2004-11-15 | 2010-12-16 | Ceptyr, Inc. | Protein tyrosine phosphatase inhibitors and methods of use thereof |
US8101745B2 (en) | 2004-12-16 | 2012-01-24 | The Regents Of The University Of California | Lung-targeted drugs |
US8071574B2 (en) * | 2005-02-22 | 2011-12-06 | John Dennis Bobyn | Implant improving local bone formation |
US20060219637A1 (en) * | 2005-03-29 | 2006-10-05 | Killeen Kevin P | Devices, systems and methods for liquid chromatography |
US20090156545A1 (en) * | 2005-04-01 | 2009-06-18 | Hostetler Karl Y | Substituted Phosphate Esters of Nucleoside Phosphonates |
US8642577B2 (en) * | 2005-04-08 | 2014-02-04 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of poxvirus infections |
EP2842559A3 (en) | 2005-04-08 | 2015-03-18 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of viral infections and other medical disorders |
AU2006239677A1 (en) * | 2005-04-25 | 2006-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of compounds to enhance processivity of telomerase |
US7914810B2 (en) * | 2005-05-06 | 2011-03-29 | Synthes Usa, Llc | Methods for the in situ treatment of bone cancer |
US8114843B2 (en) | 2005-11-18 | 2012-02-14 | The Regents Of The University Of California | Photoreactive regulator of protein function and methods of use thereof |
JP5320284B2 (ja) * | 2006-05-03 | 2013-10-23 | キメリクス,インコーポレーテッド | 抗ウイルス性または抗増殖性のホスホネート、ヌクレオシドホスホネートおよびヌクレオシドホスフェートの代謝安定性アルコキシアルキルエステル |
CN101678122A (zh) * | 2007-04-27 | 2010-03-24 | 奇默里克斯公司 | 在核苷给药的受体中降低肾中毒性的方法 |
EP2234623A4 (en) * | 2007-12-27 | 2012-03-28 | Epiphany Biosciences | ANTIVIRAL CONNECTIONS |
AU2009206673B2 (en) | 2008-01-25 | 2015-04-23 | Chimerix, Inc. | Methods of treating viral infections |
UA103329C2 (ru) | 2008-07-08 | 2013-10-10 | Гилиад Сайенсиз, Инк. | Соли соединений-ингибиторов вич |
US8628812B2 (en) | 2008-12-30 | 2014-01-14 | Pepsico, Inc. | Preservative system for acidic beverages based on sequestrants |
EP2270021A1 (en) * | 2009-06-18 | 2011-01-05 | Centre National de la Recherche Scientifique | Phosphonates synthons for the synthesis of phosphonates derivatives showing better bioavailability |
WO2011005510A2 (en) * | 2009-06-22 | 2011-01-13 | Cerapedics, Inc. | Peptide conjugates and uses thereof |
US8614200B2 (en) | 2009-07-21 | 2013-12-24 | Chimerix, Inc. | Compounds, compositions and methods for treating ocular conditions |
BR112012002551A2 (pt) | 2009-08-03 | 2017-06-13 | Chimerix Inc | composição e métodos de tratamento de infecções virais e tumores induzidos por vírus |
MX2012003914A (es) * | 2009-10-02 | 2012-05-08 | Metodo para la fabricacion de acidos aminohidroxi difosfonicos. | |
PT2534150T (pt) | 2010-02-12 | 2017-05-02 | Chimerix Inc | Métodos para tratar uma infecção viral |
AU2011239560B2 (en) | 2010-04-14 | 2016-11-03 | The Regents Of The University Of California | Phosphonates with reduced toxicity for treatment of viral infections |
EP2563367A4 (en) | 2010-04-26 | 2013-12-04 | Chimerix Inc | METHODS OF TREATING RETROVIRAL INFECTIONS AND ASSOCIATED DOSAGE REGIMES |
AU2015201895B2 (en) * | 2010-08-31 | 2016-11-17 | Emergent Biodefence Operations Lansing Llc | Phosphonate ester derivatives and methods of synthesis thereof |
RU2581045C2 (ru) * | 2010-08-31 | 2016-04-10 | Чимерикс, Инк. | Производные эфиров фосфоновых кислот и способы их синтеза |
US8884027B2 (en) | 2010-10-22 | 2014-11-11 | University Of Rochester | Melampomagnolide B derivatives as antileukemic and cytotoxic agents |
BR112014004716A2 (pt) * | 2011-08-31 | 2017-03-28 | Mallinckrodt Llc | montagem remota de nanopartículas direcionadas usando reações de hidrofosfonilação -eno/-ino de h-fosfonato |
EP3578563B1 (en) | 2011-12-22 | 2021-04-14 | Geron Corporation | Guanine analogs as telomerase substrates and telomere length affectors |
US20150209273A1 (en) * | 2012-08-28 | 2015-07-30 | Glaxosmithkline Llc | Pharmaceutical Compositions |
EP2970346B1 (en) * | 2013-03-15 | 2018-08-08 | The Regents of the University of California | Acyclic nucleoside phosphonate diesters |
MX362752B (es) | 2013-11-15 | 2019-02-07 | Chimerix Inc | Formas mórficas de ésteres de hexadeciloxipropil-fosfonato. |
JP2017512183A (ja) | 2014-02-13 | 2017-05-18 | リガンド・ファーマシューティカルズ・インコーポレイテッド | プロドラッグ化合物およびそれらの使用 |
CA2940283C (en) | 2014-03-14 | 2021-03-30 | Alltech, Inc. | Compositions of selenoorganic compounds and methods of use thereof |
EP3164136A4 (en) | 2014-07-02 | 2018-04-04 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and uses therof |
HRP20220651T1 (hr) | 2014-09-15 | 2022-08-19 | The Regents Of The University Of California | Nukleotidni analozi |
US10160778B2 (en) | 2014-10-27 | 2018-12-25 | Concert Pharmaceuticals, Inc. | Pyrimidine phosphonic acid esters |
CN112209980B (zh) | 2015-03-06 | 2023-12-05 | 阿堤亚制药公司 | 取代的嘌呤核苷酸 |
AU2016255725B2 (en) * | 2015-04-27 | 2021-09-23 | The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center | EGR1 targeting molecules for the treatment of inflammatory and hyperproliferative conditions |
WO2017048252A1 (en) | 2015-09-15 | 2017-03-23 | Alltech, Inc. | Compositions of selenoorganic compounds and methods of use thereof |
EP3350191B9 (en) | 2015-09-15 | 2021-12-22 | The Regents of the University of California | Nucleotide analogs |
RU2628456C1 (ru) * | 2016-06-29 | 2017-08-17 | Федеральное Государственное Бюджетное Учреждение Науки Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук (Имб Ран) | Новые пиримидиновые ингибиторы репликации аденовируса человека |
LU100724B1 (en) | 2016-07-14 | 2018-07-31 | Atea Pharmaceuticals Inc | Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
KR20220146668A (ko) | 2016-09-07 | 2022-11-01 | 아테아 파마슈티컬즈, 인크. | Rna 바이러스 치료를 위한 2'-치환된-n6-치환된 퓨린 뉴클레오티드 |
ES2969496T3 (es) | 2017-08-01 | 2024-05-20 | Gilead Sciences Inc | Formas cristalinas de ((S)-((((2R,5R)-5-(6-amino-9H-purin-9-il)-4-fluoro-2,5-dihidrofuran-2- il)oxi)metil)(fenoxi)fosforil)-L-alaninato de etilo para tratar infecciones virales |
RU2670204C1 (ru) * | 2017-12-01 | 2018-10-19 | федеральное государственное бюджетное учреждение "Национальный исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. Гамалеи" Министерства здравоохранения Российской Федерации | Производные 2-тиоурацила, обладающие противоаденовирусной активностью |
WO2019120084A1 (zh) * | 2017-12-21 | 2019-06-27 | 深圳市塔吉瑞生物医药有限公司 | 用于抗病毒的核苷类逆转录酶抑制剂 |
JP2021509907A (ja) | 2018-01-09 | 2021-04-08 | リガンド・ファーマシューティカルズ・インコーポレイテッド | アセタール化合物およびその治療的使用 |
US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
WO2021173713A1 (en) | 2020-02-27 | 2021-09-02 | Atea Pharmaceuticals, Inc. | Highly active compounds against covid-19 |
CN116323630A (zh) | 2020-08-24 | 2023-06-23 | 吉利德科学公司 | 磷脂化合物及其用途 |
TWI811812B (zh) | 2020-10-16 | 2023-08-11 | 美商基利科學股份有限公司 | 磷脂化合物及其用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1944530A (en) * | 1929-04-08 | 1934-01-23 | Ig Farbenindustrie Ag | Phosphoric acid esters |
GB1280788A (en) * | 1970-02-27 | 1972-07-05 | Thomae Gmbh Dr K | 3-octadecyloxypropyl-2'-trimethylammonium-ethyl phosphate |
EP0632048A1 (en) * | 1993-06-29 | 1995-01-04 | Mitsubishi Chemical Corporation | Phosphonate-nucleotide ester derivatives |
US5627185A (en) * | 1994-11-23 | 1997-05-06 | Gosselin; Gilles | Acyclovir derivatives as antiviral agents |
EP0897709A1 (en) * | 1996-12-19 | 1999-02-24 | Kao Corporation | Coating composition for teeth |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5223263A (en) * | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
FR2586685B1 (fr) * | 1985-09-03 | 1987-12-11 | Protex Manuf Prod Chimiq | Procede de preparation de nouveaux agents dispersants cationiques |
FI83421C (fi) * | 1989-06-21 | 1991-07-10 | Huhtamaeki Oy | Foerfarande foer framstaellning av farmakologiskt anvaendbara metylenbisfosfonsyraderivat. |
US5411947A (en) * | 1989-06-28 | 1995-05-02 | Vestar, Inc. | Method of converting a drug to an orally available form by covalently bonding a lipid to the drug |
US5463092A (en) * | 1989-11-22 | 1995-10-31 | Vestar, Inc. | Lipid derivatives of phosphonacids for liposomal incorporation and method of use |
ATE167679T1 (de) | 1990-09-14 | 1998-07-15 | Acad Of Science Czech Republic | Wirkstoffvorläufer von phosphonaten |
EP0477454A1 (en) * | 1990-09-28 | 1992-04-01 | Merrell Dow Pharmaceuticals Inc. | Novel phosphonate derivatives of certain nucleosides |
US5672697A (en) * | 1991-02-08 | 1997-09-30 | Gilead Sciences, Inc. | Nucleoside 5'-methylene phosphonates |
JPH05339280A (ja) * | 1991-04-26 | 1993-12-21 | Japan Tobacco Inc | (n−二環置換)アミノメチレンビスフォスフォン酸誘導体 |
JP3341303B2 (ja) * | 1991-07-11 | 2002-11-05 | 東レ株式会社 | メチレンジホスホン酸誘導体、その製造方法およびその医薬用途 |
US5879700A (en) * | 1991-10-15 | 1999-03-09 | Hostetler; Karl Y. | Nucleoside analogue phosphates for topical use |
CA2111670A1 (en) | 1992-07-10 | 1994-01-20 | Norio Kawabe | A methanediphosphonic acid derivative, process for production thereof and use for pharmaceuticals |
JP3580377B2 (ja) * | 1993-06-29 | 2004-10-20 | 三菱化学株式会社 | ホスホナートヌクレオチドエステル誘導体 |
CH690163A5 (fr) * | 1995-07-28 | 2000-05-31 | Symphar Sa | Dérivés gem-diphosphonates substitués utiles en tant qu'agents anti-cancers. |
US5922695A (en) * | 1996-07-26 | 1999-07-13 | Gilead Sciences, Inc. | Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability |
US6686462B2 (en) * | 1997-02-28 | 2004-02-03 | The Regents Of The University Of California | Antiviral compounds and methods of administration |
CA2300910C (en) * | 1997-08-18 | 2008-02-26 | Queen's University At Kingston | Phosphono-carboxylate compounds for treating amyloidosis |
FR2781228B1 (fr) | 1998-07-16 | 2000-09-29 | Pf Medicament | Phosphonates insatures derives d'indole |
ES2300281T3 (es) * | 1999-12-03 | 2008-06-16 | The Regents Of The University Of California At San Diego | Compuestos de fosfonato. |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1944530A (en) * | 1929-04-08 | 1934-01-23 | Ig Farbenindustrie Ag | Phosphoric acid esters |
GB1280788A (en) * | 1970-02-27 | 1972-07-05 | Thomae Gmbh Dr K | 3-octadecyloxypropyl-2'-trimethylammonium-ethyl phosphate |
EP0632048A1 (en) * | 1993-06-29 | 1995-01-04 | Mitsubishi Chemical Corporation | Phosphonate-nucleotide ester derivatives |
US5627185A (en) * | 1994-11-23 | 1997-05-06 | Gosselin; Gilles | Acyclovir derivatives as antiviral agents |
EP0897709A1 (en) * | 1996-12-19 | 1999-02-24 | Kao Corporation | Coating composition for teeth |
Non-Patent Citations (1)
Title |
---|
Bisphosphonate Prodrugs: Synthesis and in Vitro Evalutation of Novel Acyloxyalkyl Esters of Clodronic acid;Riku Niemi, et al;《J. Med. Chem》;19991202;第 42卷(第24期);5053-5058 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US12023348B2 (en) | 2016-04-26 | 2024-07-02 | The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center | EGR1 targeting molecules for the treatment of inflammatory and hyperproliferative conditions |
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